Primary Amine Stabilization of a Dicopper(III) Bis(μ-oxo) Species: Modeling the Ligation in pMMO

Abstract

Here we report the formation of the first examples of dicopper(III) bis(μ-oxo) complexes ligated by the primary amines, propylenediamine, and N,N,-dimethyl propylenediamine. Stabilization of these new compounds is effected at -125 °C by "core capture"- introduction of exogenous ligand to a preformed dicopper(III) bis(μ-oxo) complex supported by the peralkylated tetramethyl propylenediamine. Primary amine ligation in these compounds matches the single primary amine coordination of the putative active site of particulate methane monooxygenase (pMMO) and polysaccharide monooxygenase. Reactivity studies presented here show primary amine ligated cores are competent oxidants, capable of activating C-H bonds by an H-atom abstraction mechanism. Trends in spectroscopy, structure, and reactivity provide hints to the potential role of primary amine ligation in pMMO: increased substrate accessibility to the redox active orbitals of the Cu2O2 core and greater stabilization of the oxidant without attenuation of oxidizing power.

A tale of two methane monooxygenases

“…5), suggesting that such a species could participate in methane oxidation by pMMO. Similarly, dicopper complexes assembled using either primary amines or histamine ligands to yield a planar bis(μ-oxide) ${\text{Cu}}_2^{\text{III}}$ coordination exhibit short Cu–Cu distances and strong Cu–N bonding, and are able to oxidize hydrocarbons with C–H bond strengths of ~76 kcal/mol [150, 151]. These compounds demonstrate that histidine imidazoles can stabilize Cu III ligation under the conditions employed, and may provide a chemical rationale for the presence of an N-terminal histidine ligand in pMMO (as well as LPMO).…”

Elaboration of copper–oxygen mediated C–H activation chemistry in consideration of future fuel and feedstock generation

“…The dicopper(III) complex O seems to be most stable among the three, possibly due to the strong Cu III -oxo bonds, but the nature of the chelating ligand employed controls the chemistry and final structure. However, O is well known to attack exogenous substrates, including C–H bonds, in a wide variety of reactions as outlined by Stack, Tolman, Itoh and others [28,33-36]. …”

“…An important recent contribution from Stack and coworkers [36] establishes the chemistry of complexes O when ligated by a bidentate ligands where at least one donor is a primary amine (-NH 2 ) (Figure 3). A combination of experimental and computational studies leads to conclusions that might not be expected – the smaller size of the –NH 2 ligand (relative to – NR 2 ) allows for tight/strong Cu-N bonding and achievement of Cu high-valency in O , without loss of oxidative power.…”

Chemical Plausibility of Cu(III) with Biological Ligation in pMMO

“…16,17 We have recently described low-temperature ligand exchange as a method of assembling high-valent dicopper(III) bis(μ-oxide) compounds with previously unknown, exclusive primary-amine ligation. 18 Here we present the first example of such species supported by biologically relevant histamine ligands, directly modeling the coordination sphere in pMMO. These complexes bear definite structural resemblance to the proposed binuclear enzyme active site, and their unambiguous characterization as Cu(III) compounds suggests the accessibility of the Cu(III) oxidation state in biological systems in which histidine imidazole has been postulated to be insufficiently stabilizing.…”

“…DFT transition state optimizations of the reaction of 5 with cyclohexadiene clearly show a linear approach of the substrate C−H bond, to the O−O vector in the lowest energy pathway; this association is hindered by amine alkylation ( Figure S20). 18 Primary amine ligation in pMMO could allow fast kinetics with a strong substrate C−H bond by providing substrate accessibility to oxide ligands of the active oxidant intermediate.…”